This talk was presented at the U.S. National HIV Prevention Conference in Atlanta, Georgia, in August 2001.

Willingness to Participate and Enroll in a Phase III Preventive HIV-1 Vaccine Trial

Amy E. Weber, Jacqueline M. O'Connell, Robert S. Hogg, Keith Chan, Steffanie A. Strathdee, Nancy McLean, Steve Martindale, Brian Willoughby*, Robert Remis**.

The Vanguard Project, BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada;
* Spectrum Health Care, Vancouver, BC;
** The Omega Cohort, Montreal, PQ.

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I am pleased to have the opportunity to present this study on behalf of my colleagues as listed on this slide.

BACKGROUND:

  • Several preventive HIV candidate vaccines have entered phase I and II clinical trials
  • The first phase III HIV vaccine trial began in 1998
  • Characterising high risk populations willing to participate is important for assessing the feasibility of large-scale efficacy trials

 

By way of background it is important to point out that several preventive HIV candidate vaccines have entered phase I and II clinical trials. The first phase III HIV vaccine trial began in 1998 and is currently ongoing with Vancouver being one of over 50 sites. Finally, the characterisation of high risk populations willing to participate is important for assessing the feasibility of future large-scale efficacy trials

OBJECTIVES:

  • To assess the extent to which HIV-negative cohort study participants would be willing to participate in future HIV vaccine trials
  • To explore enrollment into an ongoing phase III HIV vaccine trial
  • To assess changing willingness to participate in vaccine trials over time

 

The objectives of this study were three-fold:

First we aimed to assess the extent to which HIV-negative participants would be willing to participate in future HIV vaccine trials.

Secondly, we aimed to explore enrollment in an ongoing phase III HIV vaccine trial.

Finally we wanted to assess changing willingness to participate in vaccine trials over time.

 

THE VANGUARD PROJECT:

  • Ongoing prospective study of over 900 gay and bisexual men in the Vancouver area
  • 15 to 30 years of age at baseline
  • No previous HIV-positive test result
  • Reside in Greater Vancouver region at baseline
  • Recruited through outreach, publicity, medical clinics and physicians
  • Annual self-administered questionnaire
  • HIV testing and stored blood specimens

 

The Vanguard Project is a prospective cohort following over 900 gay and bisexual men between the ages of 15 to 30 years in the Vancouver area.

In order to be eligible for participation in the study men must:

  • have not previously tested HIV-positive
  • reside in the greater Vancouver region at baseline
  • self-identify as gay, bisexual or have sex with men

Recruitment is conducted through outreach, publicity, medical clinics and physicians

Participation in the cohort involves the completion of an annual self-administered questionnaire and HIV antibody testing

 

STATISTICAL METHODS:

  • Contingency table analyses compared subjects who were willing to participate versus unwilling subjects
  • Multivariate logistic regression analysis
  • Sub-analysis: assess changes in WTP (1997 vs. 2001)

 

We conducted conventional statistical analyses comparing continuous variables using Wilcoxon's rank-sum test, and comparing categorical variables using Chi-squared test or Fischer's exact test.

Multivariate logistic regression was used to determine predictors of willingness to participate in HIV vaccine trials.

A sub-analysis was conducted to determine changes in willingness to participate over time from 1997 to 2001.

SOCIODEMOGRAPHIC CHARACTERISTICS:
WTP
(n=214)		 Not-WTP
(n=97)		 p-value
Median age (IQR*) 27 (24-31) 29 (26-31) 0.041
Unstable Housing 35 (16%) 4 (4%) 0.003
ETHNICITY:
Caucasian 155 (74%) 69 (76%)

0.100
Aboriginal 24 (12%) 4 (4%)
Other 30 (14%) 18 (20%)
High school education 176 (83%) 80 (87%) 0.433
Income <$10,000/year 10 (7%) 3 (4%) 0.406
Sex trade work** 48 (22%) 14 (14%) 0.102
Injection drug use** 35 (16%) 6 (6%) 0.041

* Interquartile range
** In previous year

With respect to socio-demographic characteristics, men who were willing to participate were on average 2 years younger at baseline. Approximately 12% more of the men willing to participate reported unstable housing, 10% more of the men willing to participate injected drugs in the previous year.

There were no other statistically significant socio-demographic differences.

NUMBER OF PARTNERS AND UNPROTECTED ANAL SEX:
WTP
(n=214)		 Not-WTP
(n=97)		 p-value
Male sex partners* 5 (3-15) 4 (1-12) 0.040
 
REGULAR PARTNER* (n=152) (n=80)
Anal insertive 80 (68%) 38 (61%) 0.341
Anal receptive 77 (70%) 42 (68%) 0.758
 
CASUAL PARTNER* (n=165) (n=67)
Anal insertive 45 (46%) 18 (36%) 0.228
Anal receptive 35 (42%) 7 (22%) 0.043
 
HIV-POSITIVE PARTNER* (n=36) (n=14)
Anal sex 10 (5%) 2 (2%) 0.352

* In previous year

This slide depicts reported unprotected anal sex for men reporting regular and casual partners in the year prior to baseline.

On average, men who were willing to participate reported more male sexual partners. 20% more of the men willing to participate reported unprotected receptive anal sex with casual partners.

 

SOCIAL AND EMOTIONAL STABILITY:
WTP
(n=214)		 Not-WTP
(n=97)		 p-value
Median CES-D score (IQR) 7 (3-11) 5 (2-8) 0.012
Median Rosenberg score 31 (27-35) 33 (29-37) 0.053
Median # of HIV tests 2 (1-3) 1 (1-2) 0.112

With respect to social and emotional characteristics, men who were willing to participate had on average more depressive symptoms including CES-D and Rosenberg Self-esteem scales.

There was no statistical difference in the numbers of HIV tests reported by men in the two groups.

BELIEFS ABOUT H.I.V.:
WTP
(n=214)		 Not-WTP
(n=97)		 p-value
I'm less worried about HIV infection than I used to be 40 (32%) 23 (4%) <0.001
If every HIV-positive person took the new treatments, the AIDS epidemic would be over 16 (8%) 1 (1%) 0.021
People with an undetectable viral load don't need to worry so much about infecting others with HIV 19 (9%) 2 (2%) 0.027
New HIV treatments will take the worry out of sex 31 (15%) 6 (7%) 0.035
 
Possibly, probably or most likely infected with HIV in the past year 31 (15%) 5 (5%) 0.018

This slide shows selected results from an 11 question optimism scale that has been adopted from Australia. 28% more of the men who were willing to participate reported being less worried about HIV infection than they used to be. 8% more of the men willing to participate reported that they believed that new HIV treatments will take the worry out of sex. 7% more of the men willing to participate reported that if every HIV-positive person took the new treatments, the AIDS epidemic would be over and 7% more reported that people with an undetectable viral load don't need to worry as much about infecting others with HIV.

10% more of the men willing to participate reported that they felt they were possibly, probably or most likely infected with HIV in the past year.

 

BELIEFS ABOUT VACCINE TRIAL:
WTP
(n=214)		 Not-WTP
(n=97)		 p-value
Ever heard of vaccine trial 80 (37%) 57 (59%) <0.001
Likelihood of unsafe sex...
...FOR OTHERS:

 
Much more likely 15 (19%) 6 (11%)

0.115
Somewhat more likely 41 (52%) 25 (45%)
Not more likely 18 (23%) 15 (27%)
...FOR SELF:

 
Much more likely 3 (4%) 0 (0%)

0.593
Somewhat more likely 6 (8%) 5 (9%)
Not more likely 67 (85%) 47 (84%)

Interestingly, men who expressed willingness to participate in an HIV vaccine trial were less likely to have heard about the current AIDSVAX clinical trial.

There were no significant differences in the opinions of the men in the two groups on the likelihood that the vaccine trial would lead to an increase in unprotected sex wither for others or for themselves.

REASONS FOR NOT PARTICIPATING:
WTP
(n=214)		 Not-WTP
(n=97)		 p-value
Possible health problems 8 (10%) 27 (48%) 0.001
Possible infection 10 (13%) 25 (45%) 0.001
Missed deadline 26 (33%) 3 (5%) 0.001
Concern over insurance 1 (1%) 7 (13%) 0.009
Worried about false positive 9 (11%) 13 (23%) 0.067
Concern over immigration 6 (8%) 10 (18%) 0.069
Not eligible 7 (9%) 1 (2%) 0.139
Other 26 (33%) 14 (25%) 0.321
Not at risk for HIV 14 (18%) 12 (21%) 0.590
Vaccine unlikely to work 5 (6%) 5 (9%) 0.741
Wait for more effective vaccine 13 (16%) 9 (16%) 0.978

Among individuals in our cohort who gave reasons for not enrolling in the AIDSVAX trial, almost 40% more men who were not willing to participate cited a fear of the vaccine causing health problems.

32% more of the men who were unwilling to participate cited uncertainty regarding the possibility that they may become infected from the vaccine and 12% more of the men who were unwilling to participate cited concern regarding the possibility of being denied health insurance if they tested HIV-positive as a result of being vaccinated.

There were no other statistically significant differences in reasons for not enrolling between the two groups. The most common reason for not participating among men who were willing to enroll was that they had missed the deadline for enrollment.

PREDICTORS OF WILLINGNESS TO PARTICIPATE:
Odds Ratio 95% Confidence Interval
Have a regular sex partner

0.48

0.25-0.92
Possibly or probably infected with HIV in past year

5.35

1.57-18.25

In a multivariate logistic regression model, having a regular sex partner was found to be independently associated with being less likely to be willing to participate in a HIV vaccine trial. Conversely, having a high perceived threat of HIV infection was associated with a 5-fold increase in the likelihood of being willing to participate.

TEMPORAL TRENDS IN W.T.P.:

1997:
Willing Not Willing

2001:

 Willing 63 (72%) 24 (28%)
Not Willing 3 (23%) 10 (77%)

Among 100 participants who completed questionnaires in both 1997 and 2001, 72% reported being willing to participate in both years. 23% of respondents were willing to participate in 1997 but had changed their opinions by 2001 and 28% of persons who were not willing to participate in 1997 were willing in 2001.

 


KEY FINDINGS:

  • Young gay and bisexual men who reported being willing to participate in HIV vaccine trials were:
    • Younger
    • Less stabley housed
    • Injection drug users
    • More sexually active
    • More likely to engage in risky sex
  • Varied reasons for not participating in the current trial

 

Some of the key findings of this study were that men who were willing to participate in a vaccine trial were characterised by:

  • Younger age
  • Less stabley housed
  • Injection drug users
  • More sexually active
  • More likely to engage in risky sex

A variety of reasons were offered for not participating in the current trial. Among men who were willing to participate, missing the deadline for enrollment was the most common reason.

 


LIMITATIONS:

  • Generalisability -
    • Regional variations
    • Convenience sample

 

Certain limitations should be taken into consideration when interpreting these results. Generalisability - because of regional variations and the cohort being a sample of convenience the results may not be generalisable to other populations.

However, if similar recruitment strategies are used in the future, these analyses may provide useful information on the characteristics of willing participants.

CONCLUSIONS:

  • Men who were willing to participate were characterised by:
    • Sexual risk
    • Socioeconomic disadvantage
    • High perceived threat of HIV infection
  • Evidence of a decline in interest in vaccine trial participation since 1997
  • Intensified education for community and participants required to encourage willingness to participate

 

In conclusion, the identified population may be difficult to retain, require careful monitoring and appropriate education and counselling at enrolment and throughout the trial to maximise safety for participants.

There is evidence of a decline in interest in vaccine trial participation since 1997.

Intensified education for community and participants would be required to encourage willingness to participate in future HIV vaccine trials.